7.2 Flashcards
(28 cards)
What are nuclear receptors (NRs)?
Intracellular receptors that regulate gene expression in response to ligand binding.
What biological functions are controlled by NRs?
Embryonic development, physiological homeostasis (e.g., metabolism), and disease processes.
Why are NRs important drug targets?
They regulate genes involved in metabolism, inflammation, and cancer, making them valuable for therapeutic intervention.
What is dexamethasone and its target?
A potent glucocorticoid receptor (GR) agonist used for inflammation.
What is tamoxifen and its target?
An estrogen receptor (ERα) antagonist used in breast cancer treatment.
What are thiazolidinediones (e.g., rosiglitazone)?
PPARγ agonists used to treat Type 2 Diabetes.
What is retinoic acid and its target?
A RARα agonist used in acute promyelocytic leukemia.
What is a selective nuclear receptor modulator?
A ligand that binds an NR and produces tissue-specific effects.
What determines the selective action of SNRMs?
Ligand-induced conformational changes allow binding of tissue-specific coactivators or corepressors.
What is a SERM and give an example.
Selective Estrogen Receptor Modulator; e.g., Tamoxifen.
How does tamoxifen act differently in tissues?
Antagonist in breast tissue, agonist in bone tissue.
What happens when NRs are dysfunctional?
They disrupt cellular homeostasis, leading to metabolic, developmental, and immune-related diseases.
What cancers are linked to NR dysfunction?
Breast cancer (ER), prostate cancer (AR).
What immune/inflammatory condition is linked to NR dysfunction?
Chronic inflammation via the glucocorticoid receptor.
What cardiovascular issue is associated with NR dysfunction?
Hypertension via mineralocorticoid receptor (MR).
How do NRs regulate metabolism?
By controlling gene transcription in lipid and glucose metabolism pathways.
Which NRs regulate metabolic homeostasis?
PPARs, Liver X receptor (LXR), Farnesoid X receptor (FXR), and thyroid hormone receptor.
What is metabolic syndrome?
A cluster of conditions including obesity, Type 2 Diabetes, hypertension, high triglycerides, and low HDL.
What are the 3 types of PPARs?
PPARα (liver/muscle), PPARβ/δ (ubiquitous), PPARγ (adipose tissue).
What type of receptor is PPAR?
A heterodimeric nuclear receptor (forms a complex with RXR).
What happens after ligand binding to PPAR?
Conformational change → co-repressor dissociation → co-activator binding → gene transcription.
What is PPARα’s primary role?
Promotes fatty acid utilization and ketogenesis, especially during fasting.
What drug targets PPARα?
Fibrates (e.g., fenofibrate) – used to lower triglycerides and increase HDL.
What are the downstream effects of PPARα activation?
↑ hepatic clearance of VLDL, ↑ fatty acid uptake, ↑ lipolysis, and ketone body formation.
